Although the data suggest that wood smoke exposure can also contribute to morbidity and mortality from heart disease, the current scientific knowledge base is insufficient to support causal linkage. The mechanisms by which combustion aerosol particle exposures lead to cardiovascular effects are not well understood. The proposed study will test the causal linkage between acute exposure to moderate concentrations of wood smoke and biomarkers of the risk of cardiovascular disease. It will also examine the role of monocytes in propagating inflammation and endothelial dysfunction. Increases in biomarkers of cardiovascular risk can be detected after as little as 30 minutes of exposure to combustion particles. Endothelial dysfunction is an acute effect of smoke exposure and a central contributor to vascular disease. Monocytes, which move between the respiratory tract and the vasculature, are potential activators of the endothelium. This study will use controlled human exposures to test the acute effects of wood smoke on two critical measures of cardiovascular risk: flow-mediated dilation of the brachial artery and reactive hyperemia. It will test two hypotheses: 1) endothelial dysfunction is caused by exposure to wood smoke and 2) monocytes propagate the endothelial dysfunction caused by exposure to wood smoke. The study will employ a randomized, 2-arm crossover study design in which 16 healthy subjects are exposed to pine wood smoke (at 350 g/m3 total, respirable particulate material) and to conditioned filtered air for three hours on separate days. The acute cardiovascular effects of wood smoke exposure will be assessed by measuring flow-mediated dilation of the brachial artery and reactive hyperemia. Levels of inflammatory cytokines and biomarkers of exposure will be measured. The role of monocytes in transducing signals from the respiratory epithelium to the endothelium will be evaluated by sampling central airway monocytes (via sputum induction), endothelial cells (via endothelial biopsy) and peripheral blood monocytes (via phlebotomy). Monocyte and endothelial cell populations will be purified and surface markers of apoptosis and activation will be measured using flow cytometry. This will be the first controlled human study of the effects of wood smoke exposure on flow-mediated dilation of the brachial artery, the best validated, non-invasive test of endothelial dysfunction. It will also be the first to directly assess the immediat effects of air pollutant exposure on endothelial cells in human subjects. Data from this controlled human exposure study will inform regulatory science on wood smoke and help to explain how biomass combustion particle exposures cause rapid increases in cardiovascular morbidity and mortality.